Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation

Koichi Matsuo, Jane M. Owens, Martin Tonko, Candace Elliott, Timothy J. Chambers, Erwin F. Wagner

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247 Citations (Scopus)

Abstract

Osteoclasts are bone-resorbing cells derived from haematopoietic precursors of the monocyte-macrophage lineage. Mice lacking Fos (encoding c- Fos) develop osteopetrosis due to an early differentiation block in the osteoclast lineage. c-Fos is a component of the dimeric transcription factor activator protein-1 (Ap-1), which is composed mainly of Fos (c-Fos, FosB, Fra-1 and Fra-2) and Jun proteins (c-Jun, JunB and JunD). Unlike Fra-1 (encoded by Fos/1), c-Fos contains transactivation domains required for oncogenesis and cellular transformation. The mechanism by which c-Fos exerts its specific function in osteoclast differentiation is not understood. Here we show by retroviral-gene transfer that all four Fos proteins, but not the Jun proteins, rescue the differentiation block in vitro. Structure-function analysis demonstrated that the major carboxy-terminal transactivation domains of c-Fos and FosB are dispensable and that Fra-1 (which lacks transactivation domains) has the highest rescue activity. Moreover, a transgene expressing Fra-1 rescues the osteopetrosis of c-Fos-mutant mice in vivo. The osteoclast differentiation factor Rankl (also known as TRANCE, ODF and OPGL; refs 8-11) induces transcription of Fos/1 in a c-Fos-dependent manner, thereby establishing a link between Rank signalling and the expression of Ap-1 proteins in osteoclast differentiation.

Original languageEnglish
Pages (from-to)184-187
Number of pages4
JournalNature genetics
Volume24
Issue number2
DOIs
Publication statusPublished - 2000 Feb 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Matsuo, K., Owens, J. M., Tonko, M., Elliott, C., Chambers, T. J., & Wagner, E. F. (2000). Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation. Nature genetics, 24(2), 184-187. https://doi.org/10.1038/72855